Highly potent VEGF-A-antagonistic DARPins as anti-angiogenic agents for topical and intravitreal applications.

ABSTRACT: The next-generation ophthalmic anti-VEGF therapeutics must aim at being superior to the currently available agents with regard to potency and improved drug delivery, while still being stable and safe to use at elevated concentrations. We show here the generation of a set of highly potent VEGF-A antagonistic DARPins (designed ankyrin repeat proteins) delivering these properties. DARPins with single-digit picomolar affinity to human VEGF-A were generated using ribosome display selections. Specific and potent human VEGF-A binding was confirmed by ELISA and endothelial cell sprouting assays. Cross-reactivity with VEGF-A of several species was confirmed by ELISA. Intravitreally injected DARPin penetrated into the retina and reduced fluorescein extravasation in a rabbit model of vascular leakage

SUBMITTER: Stahl A 

PROVIDER: S-EPMC3526737 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature